Background: Patients with primary liver cancer (PLC) complicated with malignant ascites (MA) have been in the end-stage of the disease (BCLC stage D or CNLC stage IV), and their survival time is less than 3 months. All guidelines recommend best supportive care (BSC), and no relative clinical trials have been involved currently. This study aims to initially explore the safety and efficacy of treatment with PD-1 monoclonal antibody (McAb) for intraperitoneal perfusion (IP) in PLC patients with malignant ascites, combined with BSC. Methods: The main inclusion criteria of this study were as follows: 1) Definitive diagnosed as advanced stage of PLC; 2) Complicated with massive MA; 3) Eastern Cooperative Oncology Group (ECOG) Performance Status was 2-3 points; 4) The expected survival time is less than 3 months. After MA fully drained, Sintilimab (PD-1 inhibitor) 100mg was injected into abdominal cavity on day 1,8,15, every 4 weeks as a cycle, until disease progression or intolerable toxicity or death of any cause. The primary endpoint was safety, while the secondary endpoint were ascites control rate (ACR), overall survival (OS), and objective response rate (ORR). Radiographic evaluation was performed using RECIST version 1.1 criteria or determined by investigator. WHO standards were used to evaluate ACR, NCI-CTC AE 4.03 grading criteria for adverse events. This study is registered with ChiCTR.org.cn ChiCTR2100043683. Results: Totally 21 cases were enrolled in this study from February 2021 to November 2022. By the last date of follow-up, 18(85.7%) cases had died. Eleven (52.4%) patients of Child-Pugh grade B, 10 (47.6%) of Child-Pugh grade C, 9 (42.9%) of ECOG2 and 12 (57.1%) of ECOG3. In terms of safety, treatment related adverse events (TRAEs) were observed in 12 (57.1%) cases, including 6 of Grade 3 (28.6%). The most common TRAEs were abdominal pain (10, 47.6%), rash (5, 23.8%), fatigue (4, 19.0%), increased blood bilirubin (3, 14.3%) and immune pituitaritis (2, 9.5%). There were no deaths observed due to TRAEs. In terms of efficacy, ACR was 43.8% (95% CI: 19.8%-70.1%) evaluated in 16 cases; The median OS was 17.6 weeks (95% CI: 8.7-79.6) in the whole group, 15.9 weeks (95% CI: 12.14-19.58) in those who had previously received PD-1 McAb for systemic therapy and 26.2 weeks in those who not received (95% CI: 14.01~38.35, P=0.717); 13 patients underwent imaging assessment, ORR was 30.8% (95%CI: 9.09%-61.43%). Conclusions: To the best of our knowledge, this study is the first IP report of clinical study on PD-1 McAb. Results showed that IP of PD-1 McAb had good safety and efficacy in end-stage PLC patients complicated with MA, and there also appears to be a control effect on liver lesions. This study is a single-arm, single-center exploratory clinical study, and a multi-center, randomized Phase III study is planned for verification. Clinical trial information: ChiCTR2100043683.